Healthy
Conditions
Keywords
no clinically relevant abnormalities
Brief summary
A Phase 1, single center, single arm, open-label study to assess the PK, safety and tolerability of Aztreonam-Avibactam after single and repeated IV infusion of doses in healthy Chinese participants.
Interventions
500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Chinese male and female participants * No clinical relevant abnormalities * willing and able to comply with all study procedures * BMI:17.5-30.5 * Sign informed consent
Exclusion criteria
* Any clinical significant illness * History of alcohol abuse * Use within 14 days prior the first study dose * CL\>80ml/min * Abnormal vital signs, such 12-ECG, blood pressure and pulse rate * Blood donation within 60days * History of HIV, HBsAg, HBcAb, HCVAb * Other medical or psychiatric may inappropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. |
| Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam | Post dose on day 1 | The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam | Post dose on day 1 | The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Aztreonam | Post dose on day 4 | AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Avibactam | Post dose on day 4 | AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
| Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Aztreonam | Post dose on day 4 | AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage. |
| Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Avibactam | Post dose on day 4 | AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage. |
| Renal Clearance (CLr) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
| Renal Clearance (CLr) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Electrocardiograms (ECGs) | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) | ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline. |
| Clearance (CL) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage. |
| Number of Participants With Abnormal Laboratory Assessments | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (basophils); clinical chemistry (urate); urinalysis (urine hemoglobin, nitrite, urine erythrocytes). |
| Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. |
| Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. |
| Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | Apparent volume of distribution (Vz) was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage. |
| Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage. |
| Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage. |
| Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage. |
| Clearance (CL) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage. |
| Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam | Post dose on day 1 and day 4 | Tmax was defined as time to reach maximum observed plasma concentration. |
| Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam | Post dose on day 1 and day 4 | Tmax was defined as time to reach maximum observed plasma concentration. |
| Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam | Post dose on day 4 | Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage. |
| Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam | Post dose on day 4 | Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage. |
| Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam | Post dose on day 4 | Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
| Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam | Post dose on day 4 | Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage. |
| Number of Participants With an Adverse Event (AE) | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. |
| Number of Participants With Abnormal Vital Signs | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) | Criteria for vital signs abnormalities: increase or decrease from baseline in supine Systolic Blood Pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in supine Diastolic Blood Pressure (DBP) \>=20 mm Hg. |
Countries
China
Participant flow
Pre-assignment details
A total of 12 participants received assigned treatment of AZTREONAM-AVIBACTAM (ATM-AVI) and completed the treatment and follow-up phases.
Participants by arm
| Arm | Count |
|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | AZTREONAM-AVIBACTAM (ATM-AVI) |
|---|---|
| Age, Continuous | 27.08 Years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam
AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam | Day 1 | 47.33 ug*hr/mL | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam | Day 4 | 49.47 ug*hr/mL | Geometric Coefficient of Variation 18 |
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam
AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam | Day 1 | 289.6 ug*hr/mL | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam | Day 4 | 337.5 ug*hr/mL | Geometric Coefficient of Variation 15 |
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam
The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam | 42.36 ng*hr/mL | Geometric Coefficient of Variation 15 |
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam
The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam | 236.7 nanograms/millilitre/hour (ng*hr/mL) | Geometric Coefficient of Variation 14 |
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Avibactam
AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Avibactam | 44.41 ug*hr/mL | Geometric Coefficient of Variation 16 |
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Aztreonam
AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Aztreonam | 285.2 ug*hr/mL | Geometric Coefficient of Variation 14 |
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam | Day 1 | 47.29 ug*hr/mL | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam | Day 4 | 49.59 ug*hr/mL | Geometric Coefficient of Variation 18 |
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam | Day 1 | 289.2 ug*hr/mL | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam | Day 4 | 337.6 ug*hr/mL | Geometric Coefficient of Variation 15 |
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam
AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam | Day 1 | 47.23 ug*hr/mL | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam | Day 4 | 49.47 ug*hr/mL | Geometric Coefficient of Variation 18 |
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam
AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam | Day 1 | 287.8 ug*hr/mL | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam | Day 4 | 336.4 ug*hr/mL | Geometric Coefficient of Variation 15 |
Primary
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam
Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam | Day 1 | 13.93 ug/mL | Geometric Coefficient of Variation 16 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam | Day 4 | 14.03 ug/mL | Geometric Coefficient of Variation 14 |
Primary
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam
Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam | Day 1 | 69.44 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam | Day 4 | 79.66 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 12 |
Primary
Renal Clearance (CLr) on Day 1 & 4 of Avibactam
CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Renal Clearance (CLr) on Day 1 & 4 of Avibactam | Day 1 | 12.09 litre per hour (L/hr) | Geometric Coefficient of Variation 18 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Renal Clearance (CLr) on Day 1 & 4 of Avibactam | Day 4 | 12.65 litre per hour (L/hr) | Geometric Coefficient of Variation 25 |
Primary
Renal Clearance (CLr) on Day 1 & 4 of Aztreonam
CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Renal Clearance (CLr) on Day 1 & 4 of Aztreonam | Day 1 | 4.277 litre per hour (L/hr) | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Renal Clearance (CLr) on Day 1 & 4 of Aztreonam | Day 4 | 4.487 litre per hour (L/hr) | Geometric Coefficient of Variation 23 |
Primary
Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Avibactam
AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Avibactam | 177.7 ug*hr/mL | Geometric Coefficient of Variation 16 |
Primary
Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Aztreonam
AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Aztreonam | 1142 ug*hr/mL | Geometric Coefficient of Variation 14 |
Secondary
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam
Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam | 1.049 ratio | Geometric Coefficient of Variation 6 |
Secondary
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam
Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam | 1.204 ratio | Geometric Coefficient of Variation 6 |
Secondary
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam
Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam | 1.006 ratio | Geometric Coefficient of Variation 7 |
Secondary
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam
Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam | 1.149 ratio | Geometric Coefficient of Variation 5 |
Secondary
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam | Day 1 | 21.36 Liter | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam | Day 4 | 17.96 Liter | Geometric Coefficient of Variation 16 |
Secondary
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam
Apparent volume of distribution (Vz) was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam | Day 1 | 13.69 Liter | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam | Day 4 | 12.81 Liter | Geometric Coefficient of Variation 15 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam | Day 1 | 30.14 Liter | Geometric Coefficient of Variation 22 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam | Day 4 | 65.41 Liter | Geometric Coefficient of Variation 26 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam | Day 1 | 14.09 Liter | Geometric Coefficient of Variation 16 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam | Day 4 | 14.22 Liter | Geometric Coefficient of Variation 16 |
Secondary
Clearance (CL) on Day 1 & 4 of Avibactam
CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Clearance (CL) on Day 1 & 4 of Avibactam | Day 1 | 10.56 litre per hour (L/hr) | Geometric Coefficient of Variation 15 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Clearance (CL) on Day 1 & 4 of Avibactam | Day 4 | 11.26 litre per hour (L/hr) | Geometric Coefficient of Variation 16 |
Secondary
Clearance (CL) on Day 1 & 4 of Aztreonam
CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Clearance (CL) on Day 1 & 4 of Aztreonam | Day 1 | 5.188 litre per hour (L/hr) | Geometric Coefficient of Variation 14 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Clearance (CL) on Day 1 & 4 of Aztreonam | Day 4 | 5.261 litre per hour (L/hr) | Geometric Coefficient of Variation 14 |
Secondary
Number of Participants With Abnormal Electrocardiograms (ECGs)
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline.
Time frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (msec): %Change >= 25/50% | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (msec): %Change >= 50% | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (msec): 30 < Change <= 60 | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (msec): Change > 60 | 0 Participants |
Secondary
Number of Participants With Abnormal Laboratory Assessments
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (basophils); clinical chemistry (urate); urinalysis (urine hemoglobin, nitrite, urine erythrocytes).
Time frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Laboratory Assessments | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2x upper limit of normal (ULN) | 1 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Laboratory Assessments | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2x ULN | 1 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Laboratory Assessments | URINALYSIS: URINE Hemoglobin >= 1 | 3 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Laboratory Assessments | URINALYSIS: URINE Erythrocytes >= 20 | 2 Participants |
Secondary
Number of Participants With Abnormal Vital Signs
Criteria for vital signs abnormalities: increase or decrease from baseline in supine Systolic Blood Pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in supine Diastolic Blood Pressure (DBP) \>=20 mm Hg.
Time frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Vital Signs | Supine Diastolic Blood Pressure (mmHg): Change >= 20 mmHg increase from baseline | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Vital Signs | Supine Systolic Blood Pressure (mmHg): Change >= 30 mmHg increase from baseline | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Vital Signs | Supine Diastolic Blood Pressure (mmHg): Change >= 20 mmHg decrease from baseline | 0 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With Abnormal Vital Signs | Supine Systolic Blood Pressure (mmHg): Change >= 30 mmHg decrease from baseline | 0 Participants |
Secondary
Number of Participants With an Adverse Event (AE)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Time frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With an Adverse Event (AE) | Participants with treatment-emergent adverse events (all-causality) | 2 Participants |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Number of Participants With an Adverse Event (AE) | Participants with treatment-emergent adverse events (treatment-related) | 1 Participants |
Secondary
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam | Day 1 | 2.003 hours | Standard Deviation 0.34613 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam | Day 4 | 4.061 hours | Standard Deviation 0.5918 |
Secondary
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam | Day 1 | 1.890 hours | Standard Deviation 0.16597 |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam | Day 4 | 1.886 hours | Standard Deviation 0.20304 |
Secondary
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam
Tmax was defined as time to reach maximum observed plasma concentration.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam | Day 1 | 2.44 hours |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam | Day 4 | 2.46 hours |
Secondary
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam
Tmax was defined as time to reach maximum observed plasma concentration.
Time frame: Post dose on day 1 and day 4
Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AZTREONAM-AVIBACTAM (ATM-AVI) | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam | Day 1 | 2.92 hours |
| AZTREONAM-AVIBACTAM (ATM-AVI) | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam | Day 4 | 2.92 hours |